Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis

Alcoholic Hepatitis Clinical Trial

— RIFA-AAH  

Official title:

Effects of Rifaximin Treatment in Patients With Acute Alcoholic Hepatitis: A Comparative Pilot Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02116556
• Other study ID #: RIFA-AAH.
• Status: Enrolling by invitation
• Phase: Phase 2
• First received: April 15, 2014
• Last updated: November 3, 2016
• Start date: April 2013
• Est. completion date: December 2016

Study information

• Verified date: November 2016
• Source: Hospital Universitari Vall d'Hebron Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

Acute alcoholic hepatitis (AAH) is a serious condition and one of the most frequent causes of Acute-on-Chronic Liver Failure. The current standard therapy (corticosteroids) is theme of debate and unsatisfactory in many patients (year mortality: 30%). One of the main causes of death is bacterial infections, which affect 40-50% of patients at 90 days. Intestinal decontamination with rifaximin (a nonabsorbable antibiotic) reduces endotoxemia, improves liver function and reduces the complications of decompensated alcoholic cirrhosis.

The Hypothesis/Objective: To assess whether oral decontamination with rifaximin prevents the development of infections associated with AAH and analyze its consequences.

Description:

Design: Open multicenter comparative study. A cohort (n = 66) will receive rifaximin (1200 mg / d) for 90 days. Results will be compared with those of a cohort of AAH prospectively included in an observational study. Both groups with a uniform treatment protocol (which includes the administration of corticosteroids and standardized treatment for complications of liver failure). Patients will be monitorized until hospital discharge and a follow-up visit at 7, 30, 45, 60 and 90 days will be performed.

Endpoints:

1. Primary endpoint: Bacterial infections after 90 days.

2. Secondary endpoints: :

2.1. Liver function tests 2.2. Levels of endotoxemia 2.3. Complications of liver cirrhosis. 2.4. Survival

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 29
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients =18 and <70 years of age.

• Active alcohol abuse and excessive alcohol consumption prior to admission defined as > 50 g per day for men and> 40 g per day for women.

• Jaundice (Bilirubin >2 mg/dl) for no more than 3 months.

• Clinical suspicion of Alcoholic Hepatitis with a modified Maddrey's Discriminant Function > 32 points.

Exclusion Criteria:

• Hypersensitivity to Rifaximin

• Advanced Chronic or Terminal illness. Advanced Chronic illness will be defined as:

all conditions evolved into a clinical stage to limit the patient's functional status (eg, heart failure NYHA> II, COPD PCO2> 50 mmHg or PO2 <60 mmHg, stroke or other disabling neurological disease, disabling or uncontrolled oncological conditions, etc ...).

Terminal illness will be defined as any clinical conditions with a survival expectancy less than 3 months

• Hepatocellular carcinoma (previously diagnosed) beyond Milan's criteria.

• Complete portal vein thrombosis (previously diagnosed).

• Autoimmune liver disease.

• Hepatitis B and C and HIV infection (anti-HCV, surface HBV antigen and anti-HIV positive).

• Pregnancy or nursing.

• Use of Rifaximin during the previous 2 months.

• Treatment with Pentoxifylline.

• Lack of informed consent.

Removal criteria:

• Lack of histological confirmation of Alcoholic Hepatitis during the first 7 days after inclusion.

Because there are no non-diagnostic tools to diagnose alcoholic hepatitis, histological confirmation is required in all patients (preferably through a transjugular biopsy): alcoholic hepatitis will be diagnosed on the presence of the following histologic features:

Hepatocellular damage (eg, hepatocyte ballooning and presence of Mallory-Denk bodies).

Inflammatory infiltrate (predominantly polymorphonuclear cells). Pericellular or sinusoidal fibrosis.

• Hepatocellular carcinoma beyond Milan's criteria diagnosed during the first 7 days after inclusion.

• Complete portal vein thrombosis diagnosed during the first 7 days after inclusion.

• Protocol violation.

• Severe adverse event directly related with Rifaximin.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alcoholic Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic

Intervention

Drug:
• Prednisone
Prednisone PO 40mg/day or IV equivalent dosage for 30 days. Patients not responding at 7 days (e.g. Lille Model = 0.45) treatment with Prednisone will be suspended.
• Rifaximin
Rifaximin PO 1200 mg/day for 90 days

Locations

Country	Name	City	State
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari Germans Trias i Pujol	Barcelona
Spain	Vall d'Hebron Hospital	Barcelona

Sponsors (4)

Lead Sponsor	Collaborator
Hospital Universitari Vall d'Hebron Research Institute	Germans Trias i Pujol Hospital, Hospital de Sant Pau, Hospital del Mar

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Endotoxemia serum levels	Measurement of serum changes in endotoxemia levels during the rifaximin treatment.	90 days	No
Primary	Rate of bacterial infections	Development of any bacterial infection.	90 days	No
Secondary	Rate of Decompensations of Liver Cirrhosis	Development of any liver cirrhosis decompensations; Hepatic Encephalopathy; Acute Kidney Injury (including Hepatorenal Syndrome); Acute variceal bleeding; Ascites; Death	90 days	No